Photodynamic therapy (PDT) refers to the use of photosensitizing drugs in combination with light for treating medical conditions. The PDT technique has shown promise as a cancer therapy (Dolmans, D. E., Fukumura, D., and Jain, R. K. (2003). Photodynamic therapy for cancer. Nat. Rev. Cancer 3, 380-387) and recently has achieved success as a treatment for age-related macular degeneration (Brown, S. B., and Mellish, K. J. (2001). Verteporfin: a milestone in opthalmology and photodynamic therapy. Expert Opin. Pharmacother. 2, 351-361). The PDT method uses a compound known as a photosensitizer (PS) which is administered directly (e.g., endoscopically or topically) to an accessible treatment site, or alternatively, is administered systemically and concentrates in a target tissue site within the body of a subject. Subsequent irradiation of the target site with visible light of suitable wavelength generates singlet oxygen, 1O2, within or on the surface of the cells of the treatment site, ultimately leading to cell death. The singlet oxygen is catalytically generated by energy transfer from the PS to oxygen from dissolved O2, which is ubiquitous in the body's tissues. Photodynamic therapy is advantageous compared with other therapies due to its dual selectivity: not only is the PS targeted to the tumor or other lesion, but the light can also be accurately delivered to the affected tissue.
The potential use of a photosensitizer as an effective means of killing microorganisms was first recognized over 100 years ago (Moan, J., and Peng, Q. (2003). An outline of the hundred-year history of PDT. Anticancer Res. 23, 3591-3600); however, the possible use of PDT as a treatment for microbial infections is just beginning to be appreciated (Wainwright, M. (1998). Photodynamic antimicrobial chemotherapy (PACT). J. Antimicrob. Chemother. 42, 13-28, Maisch, T., Szeimies, R. M., Jori, G., and Abels, C. (2004). Antibacterial photodynamic therapy in dermatology. Photochem. Photobiol. Sci. 3, 907-917 and 30. Hamblin, M. R., and Hasan, T. (2004). Photodynamic therapy: a new antimicrobial approach to infectious disease? Photo-chem. Photobiol. Sci. 3, 436-450). For decades, antibiotics have been the first line of defense against microorganisms. Of great concern in current medical practice is the proliferation of infectious microbes that display multiple antibiotic resistance, and hence are not killed by existing antibiotics alone or in combination. Accordingly, there is a great unmet need to develop new antimicrobial agents to which microbes are not easily able to develop resistance. In this regard, it is envisioned that treatment of infections with PDT holds great promise as an alternative or adjunct to traditional antibiotic therapy because organisms are unlikely to develop resistance to a killing mechanism based on bombardment of the pathogens with reactive oxygen species.
Given the urgent need for new antimicrobial agents, it would be desirable to develop PS compounds that are effective at killing a broad range of microbes such as bacteria, fungi and yeast but are not harmful to the cells of a mammalian subject receiving antimicribial PS therapy.